TECHNICAL FIELD

The invention relates to infusion devices and associated methods. Particularly, though not exclusively, the invention relates to infusion devices for infusing a therapeutic agent, such as insulin, to patients, such as those living with diabetes.

BACKGROUND

For patients with diabetes, insulin therapy is often an important part of their treatment, helping to regulate blood sugar levels and store excess glucose for energy. There are two principal modes for delivering insulin. The first mode includes syringes and injector pens, which are used to inject a dose of insulin typically three to four times a day (depending on, inter alia, the type of diabetes and blood sugar levels of the patient). While these devices are simple and low cost, delivering each dose of insulin requires a needle stick. The second mode uses an infusion pump, sometimes called an insulin pump, which delivers controlled doses of insulin throughout the day. An infusion pump can be used to deliver insulin to a patient continuously (basal dose), on demand (bolus dose) or at scheduled intervals. Infusion pumps are more complex and expensive than syringes and pens, though enable improved regulation of blood sugar levels, for example by programmable delivery schedules, and fewer needle sticks. The second mode is known as continuous subcutaneous insulin infusion (CSII) therapy.

Infusion pump systems for CSII therapy may be worn by the patient. The systems typically comprise a combined infusion pump and reservoir for containing an insulin drug, for example human insulin or analogue insulin, and an insulin infusion set. The infusion set may comprise a cannula (for example, a polymeric catheter or metal needle) for insertion subcutaneously into the patient and flexible tubing for fluidly connecting the cannula to the reservoir. Once the cannula is inserted into the patient, it may remain in place for a period of time, i.e. days, to allow for continuous delivery of the insulin drug. The current recommended wear time for insulin infusion sets is two to three days, to avoid problems that may arise relating to the infusion set itself or to the infusion site. However, such problems may still arise within recommended wear times, resulting in early removal of the infusion set and more frequent site rotation across infusion sites (for example buttocks, abdomen and arms).

While problems relating to the infusion set have been well investigated and addressed in recent years, there remains little understanding and few solutions to address problems relating to the infusion site. Problems relating to the infusion site include pain, bleeding, infection, skin irritation, erythema, lipohypertrophy and lipoatrophy. Problems at the infusion site may lead to the build-up of scar tissue, which consequently lowers insulin sensitivity and increases the risk of hypoglycaemia, as well as having a cosmetic impact on patients. All these problems can deter patients from continuing to use their infusion pumps, resulting in poorer patient outcomes.

It is known that problems at teh infusion site are a consequence of the immune response to the presence of the cannula and the insulin drug in the body. The immune system responds by activating and progressing the foreign body reaction (FBR) - an inflammatory and fibrotic process that occurs upon introducing a foreign material into the body. In FBR, cells of the immune system identify foreign material and attempt to degrade it, or otherwise encapsulate the material by forming a physical barrier to isolate it from the rest of the body. FBR is a problem for increasing wear times of infusion sets in CSII therapy, as the immune system reacts to the inserted cannula and the insulin drug. This limitation prevents realising the full potential of CSII therapy.

The problem presented by FBR is particularly acute in the development of so-called closed-loop systems. In closed-loop systems, am infusion pump system is used in combination with a continuous glucose monitoring (CGM) device, to continually monitor blood sugar levels and adjust the amount of insulin delivered to the patient automatically. CGM devices are already achieving 14-day wear times, and are thus currently achieving superior wear times compared to infusion sets. Generally, unwanted species, whether biological, chemical or physical, present in infusible solutions have undesirable consequences for patients.

It is an object of embodiments of the invention to provide an improved infusion device that attempts to circumvent FBR, increase wear times of infusion sets, and/or at least mitigate one or more problems associated with known arrangements.

SUMMARY OF THE INVENTION

According to an aspect of the invention, there is provided an infusion device for subcutaneous infusion of a therapeutic agent, the infusion device comprising: a reservoir for containing a therapeutic agent; and a cooling unit comprising a heat transfer surface for absorbing ambient heat (i.e. heat available from the environment and/or components surrounding the heat transfer surface), the heat transfer surface being disposed in relation to the reservoir to enable transfer of heat from the reservoir to the cooling unit.

According to another aspect of the invention, there is provided an infusion device for subcutaneous infusion of a therapeutic agent, the infusion device comprising: a reservoir compartment for receiving and at least partially supporting a reservoir within the device; and a cooling unit comprising a heat transfer surface for absorbing ambient heat, the heat transfer surface being disposed in relation to the reservoir compartment to enable transfer of heat from the reservoir compartment to the cooling unit.

According to another aspect of the invention there is provided a method of subcutaneous infusion of a therapeutic agent, the method comprising the steps of: providing the infusion device as described above; and cooling, or maintaining a temperature within, the reservoir and/or reservoir compartment prior to delivery of a therapeutic agent from the reservoir to a patient. According to another aspect of the invention, there is provided an infusion device for subcutaneous infusion of a therapeutic agent, the infusion device comprising: a reservoir for containing a therapeutic agent; and a cooling unit comprising a heat transfer surface for absorbing ambient heat, the heat transfer surface being disposed in relation to the reservoir to enable transfer of heat from the reservoir to the cooling unit, wherein the cooling unit comprises a conduit for circulating a cooling medium therethrough, the cooling conduit comprising the heat transfer surface.

According to another aspect of the invention, there is provided an infusion device for subcutaneous infusion of a therapeutic agent, the infusion device comprising: a reservoir for containing a therapeutic agent; and a cooling unit comprising a heat transfer surface for absorbing ambient heat, the heat transfer surface being disposed in relation to the reservoir to enable transfer of heat from the reservoir to the cooling unit, wherein the cooling unit comprises a conduit for circulating a cooling medium therethrough, the cooling conduit comprising the heat transfer surface, and wherein the device comprises a refrigeration unit connected to the cooling unit for lowering the temperature of the cooling medium.

According to another aspect of the invention, there is provided an infusion device for subcutaneous infusion of a therapeutic agent, the infusion device comprising: a reservoir for containing a therapeutic agent; and a cooling unit comprising a heat transfer surface for absorbing ambient heat, the heat transfer surface being disposed in relation to the reservoir to enable transfer of heat from the reservoir to the cooling unit, wherein the cooling unit comprises a conduit for circulating a cooling medium therethrough, the cooling conduit comprising the heat transfer surface, and wherein the device comprises a refrigeration unit connected to the cooling unit for lowering the temperature of the cooling medium, and wherein the device comprises a temperature sensor for sensing a temperature within the reservoir and a controller for controlling the refrigeration unit in response to the temperature. According to another aspect of the invention, there is provided an infusion device for subcutaneous infusion of a therapeutic agent, the infusion device comprising: a reservoir for containing a therapeutic agent; and a cooling unit comprising a heat transfer surface for absorbing ambient heat, the heat transfer surface being disposed in relation to the reservoir to enable transfer of heat from the reservoir to the cooling unit, wherein the device comprises a reservoir compartment for receiving and at least partially supporting the reservoir within the device.

According to another aspect of the invention, there is provided an infusion device for subcutaneous infusion of a therapeutic agent, the infusion device comprising: a reservoir for containing a therapeutic agent; and a cooling unit comprising a heat transfer surface for absorbing ambient heat, the heat transfer surface being disposed in relation to the reservoir to enable transfer of heat from the reservoir to the cooling unit, wherein the cooling unit comprises a conduit for circulating a cooling medium therethrough, the cooling conduit comprising the heat transfer surface, and wherein the device comprises a reservoir compartment for receiving and at least partially supporting the reservoir within the device.

In certain embodiments, the cooling unit may comprise a conduit for circulating a cooling medium therethrough, the cooling conduit comprising the heat transfer surface. Additionally, the infusion device may comprise a refrigeration unit connected to the cooling unit for lowering the temperature of the cooling medium. Moreover, the infusion device may comprise a temperature sensor for sensing a temperature within the reservoir and a controller for controlling the refrigeration unit in response to the temperature.

In certain embodiments, the heat transfer surface is in direct contact with a surface of the reservoir. Moreover, the reservoir and the heat transfer surface may correspond at least partially in shape to facilitate the direct contact therebetween. In certain embodiments, the cooling conduit may be provided as a coil extending around at least a portion of the reservoir.

In certain embodiments, the infusion device may comprise a reservoir compartment for receiving and at least partially supporting the reservoir within the device. The reservoir compartment may comprise a material having a heat conductivity of at least 80 W/mK. The heat transfer surface may be in direct contact with a surface of the reservoir compartment.

In certain embodiments, the reservoir compartment and the heat transfer surface may correspond at least partially in shape to facilitate the direct contact therebetween. Moreover, the cooling conduit may be provided as a coil extending around at least a portion of the reservoir compartment.

In certain embodiments, the cooling unit may at least partially support the reservoir within the device. Additionally, or alternatively, the cooling unit may at least partially support the reservoir compartment within the device.

In certain embodiments, the infusion device may comprise a fluid pump for delivering the therapeutic agent from the reservoir. Additionally, or alternatively, the infusion device may comprise an infusion set comprising tubing and a cannula for insertion into a patient, the tubing for fluidly connecting the reservoir to the cannula to deliver the therapeutic agent to the patient.

In certain embodiments, the infusion device may comprise an insulating compartment for insulating the reservoir from sources of heat. In certain embodiments, the therapeutic agent may comprise insulin.

Devices and methods according to embodiments of the invention may be useful in inhibiting FBR at an infusion site, and thereby may avoid problematic occurrences such as coagulation, occlusion and/or inflammation at the infusion site, and/or encapsulation of the cannula. In particular, devices and methods according to embodiments of the invention may be useful in inhibiting FBR at the infusion site in diabetic patients receiving CSII therapy, wherein the infusion site is a single infusion site in use for an extended period of time, for example at least four days.

Devices and methods according to embodiments of the invention may be useful in cooling a therapeutic agent prior to delivery to a patient. In particular, devices and methods according to embodiments of the invention may be useful where the therapeutic agent comprises insulin, and cooling the therapeutic agent may preserve and/or stabilise the therapeutic agent, and/or inhibit the formation of unwanted species, for example insulin agglomerates and other particulates, within the therapeutic agent, which may otherwise activate FBR at the infusion site.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments of the invention will now be described, by way of example only, with reference to the accompanying figures, in which:

Figure 1 is a schematic perspective view of an infusion device according to an embodiment of the invention;

Figure 2 is a schematic cutaway view of the infusion device of Figure 1 , shown supported in a casing; and

Figure 3 is a schematic cutaway view of an infusion device according to an embodiment of the invention.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

Embodiments of the invention have particular application for use with infusion pump systems such as an infusion pump for delivery of a therapeutic agent, the infusion pump comprising a fluid pump and a reservoir, and an infusion set having a cannula and tubing for connecting the cannula to the reservoir. However, other applications are contemplated, for example cannula access ports and alternative infusion pump systems such as patch pumps, which have no tubing. In certain embodiments, the infusion pump may be an insulin pump for CSII therapy and the therapeutic agent may be an insulin drug, for example human insulin or analogue insulin. Embodiments of the invention are intended for delivering insulin to a patient at a single infusion site over an extended period of time. Used herein, an extended period of time is to be understood to mean at least four days. More specifically, an extended period of time may include four to seven days, seven or more days, seven to 10 days, and 10 or more days. An extended period of time may include 14 or more days. Embodiments of the invention may be used in closed loop systems, wherein the extended period of time may be at least equal to the wear time and/or lifetime of a CGM device.

Figures 1 and 2 illustrate an infusion device 10 according to an embodiment of the invention. The device 10 comprises a reservoir 12 supported within a cooling unit 14. In the illustrated embodiment, the cooling unit comprises a heat transfer surface 16 in contact with an outer surface 18 of the reservoir 12 to enable the cooling unit 14 to cool a therapeutic agent contained within the reservoir 12 (i.e. by transfer of heat from the therapeutic agent to the cooling unit 14 via the reservoir 12). The therapeutic agent may be an insulin solution. The reservoir 12 has an outlet port 20 for fluidly connecting the reservoir to an infusion site, for example via an infusion set. The reservoir 12 may be a substantially cylindrical container suitable for containing the therapeutic agent. However, the reservoir 12 may be any suitable shape, for example cuboid or frustoconical. In embodiments of the invention, the reservoir 12 may be an insulin cartridge or a vial, such as a proprietary insulin cartridge for an infusion pump system. The reservoir 12 may comprise a material having a high heat conductivity property, for example a heat conductivity of at least 80 W/mK. Suitable heat conductivity may be from 80 to 200 W/mK, or even in excess of 200 W/mK. Particularly suitable heat conductivity maybe at least 100 W/mK. The reservoir 12 may comprise aluminium, or an aluminium alloy.

As above, the cooling unit 14 comprises a heat transfer surface 16. The heat transfer surface 16 is configured for absorbing ambient heat (i.e. heat available from the immediate surroundings). The heat transfer surface 16 may be provided by a conduit 22 for circulating a cooling medium therethrough. As such, the conduit 22 may provide a closed-loop for circulating the cooling medium. Suitable cooling mediums may include distilled water, an oil or mineral mixture, such as a water-glycol solution, or a refrigerant. In the illustrated embodiment, the conduit 22 is a coil extending around the outer surface of the reservoir 12 to substantially surround the reservoir 12, while leaving an opening 22a for the reservoir 12 to be received within the cooling unit 14. In certain embodiments, the conduit 22 may extend around the outer surface of the reservoir 12 in a serpentine arrangement to substantially surround the reservoir 12. Generally, the conduit 22 surrounds the outer surface of the reservoir 12 to provide direct, surface-to-surface contact between the reservoir 12 and the heat transfer surface 16. As such, the reservoir 12 and the heat transfer surface 16 typically correspond at least partially in shape to facilitate the direct contact therebetween.

In certain embodiments, the device 10 may include a component intermediate the reservoir 12 and the heat transfer surface 16, for example a reservoir compartment (not shown). The reservoir compartment may receive and at least partially support the reservoir 12 within the device 10. The reservoir compartment may support the reservoir 12 in combination with the cooling unit 14. The reservoir compartment may allow the reservoir 12 to be releasably secured within the device 10, allowing for the reservoir 12 to be removed and reintroduced, or replaced, to facilitate refilling of the reservoir 12. Although the reservoir 12 may be refilled in situ in certain embodiments. The conduit 22 may be a coil extending around an outer surface of the reservoir compartment to substantially surround the compartment. In certain embodiments, the conduit 22 may extend around the outer surface of the reservoir 12 in a serpentine arrangement to substantially surround the reservoir compartment. Generally, the conduit 22 may surround the outer surface of the reservoir compartment to provide direct, surface-to-surface contact between the reservoir compartment and the heat transfer surface 16. As such, the reservoir compartment and the heat transfer surface 16 may typically correspond at least partially in shape to facilitate the direct contact therebetween. An inner surface of the reservoir compartment may be configured to provide direct, surface-to-surface contact between the reservoir 12 and the reservoir compartment, and the reservoir 12 and the reservoir compartment may correspond at least partially in shape to facilitate the direct contact therebetween. The reservoir compartment may comprise a material having a high heat conductivity property, for example a heat conductivity of at least 80 W/mK. Suitable heat conductivity may be from 80 to 200 W/mK, or even in excess of 200 W/mK. Particularly suitable heat conductivity maybe at least 100 W/mK. The reservoir compartment may comprise aluminium, or an aluminium alloy.

The device 10 may comprise a refrigeration unit 24 connected to the cooling unit 14 for lowering the temperature of the cooling medium. The reservoir 12, the cooling unit 14 and/or the refrigeration unit 24 may be individually or collectively supported with a casing 26 (shown in Figure 2) of the device 10. The refrigeration unit 24 may include a venting part 28, open to a side of the casing 26, to allow transfer of heat from the cooling unit 14, and consequently from the device 10. To control the refrigeration unit 24, i.e. control cooling of the therapeutic agent, the device 10 may comprise a controller (not shown). The controller may control the refrigeration unit 24 in response to a temperature within the reservoir 12, for example a temperature of the therapeutic fluid. As such, the device 10 may include a temperature sensor (not shown) for sensing a temperature within the reservoir 12. The temperature sensor may be a thermistor comprising a sensing probe in direct contact with the reservoir 12 and/or or the therapeutic agent when contained within the reservoir 12. The controller may be a main controller of an infusion pump system, or an ancillary controller in communication with such a main controller. The controller may be configured to enable control by a user, directly or via a main controller, for example to start, stop, or adjust cooling of the therapeutic agent. Control of the cooling may be automatic.

The device 10 may comprise an insulating compartment (not shown) for insulating the reservoir 12 from sources of heat, such as body heat of the patient. The insulating compartment may be configured to at least partially encapsulate at least the reservoir 12 and the cooling unit 14. Suitable materials for the insulting compartment include foam materials and reflective foils.

Generally, the cooling unit is configured to facilitate the infusion of insulin at a single infusion site over an extended period of time, for example by inhibiting formulation of unwanted species in insulin solutions such as insulin agglomerates, and thereby increase wear times, for example at least four days, including four to seven days, seven or more days, seven to 10 days, 10 or more days, and 14 or more days. Cooling the insulin prior to injection may also reduce pain at the infusion site.

Figure 3 illustrates an infusion device 100 according to an embodiment of the invention comprising components of an infusion pump system. The device 100 comprises the device 10 described above with reference to Figures 1 and 2 (i.e. including the reservoir 12 and the cooling unit 14). The device 100 further comprises an infusion pump 130, which may be an insulin pump, and an infusion set 132. The infusion set 132 comprises tubing 134, a cannula 136 for insertion into an infusion site 138 (for example, the sub-dermal fatty tissue of a patient), and an infusion hub 140 for maintaining the cannula in the infusion site 138. The device 100 enables delivery of the therapeutic agent from the reservoir 12 to the patient.

Infusion sets, infusions hubs and infusion pumps suitable for use in embodiments of the invention are known in the art, and examples are disclosed in earlier patent applications, including W02007/092210, WC2010/112521 , US11197949, US5257980 and WO98/9856693, the contents of which are incorporated herein by reference. Throughout the description and claims of this specification, the words “comprise” and “contain” and variations of them mean “including but not limited to”, and they are not intended to (and do not) exclude other moieties, additives, components, integers or steps. Throughout the description and claims of this specification, the singular encompasses the plural unless the context otherwise requires. In particular, where the indefinite article is used, the specification is to be understood as contemplating plurality as well as singularity, unless the context requires otherwise.

Features, integers, characteristics, compounds, chemical moieties or groups described in conjunction with a particular aspect, embodiment or example of the invention are to be understood to be applicable to any other aspect, embodiment or example described herein unless incompatible therewith. All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and/or steps are mutually exclusive. The invention is not restricted to the details of any foregoing embodiments. The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.

Attention is directed to all papers and documents which are filed concurrently with or previous to this specification in connection with this application and which are open to public inspection with this specification, and the contents of all such papers and documents are incorporated herein by reference.